Mitophagy is required for brown adipose tissue mitochondrial homeostasis during cold challenge

Scientific Reports
Yuan LuMukesh K Jain

Abstract

Brown adipose tissue (BAT) is a specialized thermogenic organ in mammals. The ability of BAT mitochondria to generate heat in response to cold-challenge to maintain core body temperature is essential for organismal survival. While cold activated BAT mitochondrial biogenesis is recognized as critical for thermogenic adaptation, the contribution of mitochondrial quality control to this process remains unclear. Here, we show mitophagy is required for brown adipocyte mitochondrial homeostasis during thermogenic adaptation. Mitophagy is significantly increased in BAT from cold-challenged mice (4 °C) and in β-agonist treated brown adipocytes. Blockade of mitophagy compromises brown adipocytes mitochondrial oxidative phosphorylation (OX-PHOS) capacity, as well as BAT mitochondrial integrity. Mechanistically, cold-challenge induction of BAT mitophagy is UCP1-dependent. Furthermore, our results indicate that mitophagy coordinates with mitochondrial biogenesis, maintaining activated BAT mitochondrial homeostasis. Collectively, our in vivo and in vitro findings identify mitophagy as critical for brown adipocyte mitochondrial homeostasis during cold adaptation.

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Citations

Sep 21, 2018·Antioxidants & Redox Signaling·Maroua FerhatSihem Boudina
Oct 9, 2019·International Journal of Molecular Sciences·Jae Ho LeeKwang-Hee Bae
Jan 24, 2020·Antioxidants & Redox Signaling·Lei LiuQuan Chen
May 14, 2019·The Journal of Clinical Investigation·Haidong YuTamás Röszer
Apr 30, 2020·International Journal of Molecular Sciences·Winifred W Yau, Paul M Yen
Dec 8, 2019·Journal of Physiology and Biochemistry·Montserrat Cairó, Joan Villarroya
Jan 14, 2021·International Journal of Molecular Sciences·Lucia A SealeMarla J Berry
Jun 3, 2021·Cells·Francesca MolinariAndrea Armani

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Datasets Mentioned

BETA
ABE4837

Methods Mentioned

BETA
PCR
fluorescence imaging
transgenic
ubiquitination
protein assay

Software Mentioned

NIH image J
GeneGlobe Data Analysis Center
NeuroScore

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